title: Mechanistic study on the cleavage and reorganization of C(sp3)-H and C=N bonds in carbodiimides: synthesis of 1,2-dihydrothiopyrimidines and 2,3-dihydropyrimidinthiones through four-component coupling.
abstract: This study sheds light on the cleavage and reorganization of C(sp(3))-H and C=N bonds of carbodiimides in a three-component reaction of terminal alkynes, sulfur, and carbodiimides by a combination of methods including 1) isolation and X-ray analysis of six-membered-ring lithium species 2-S, 2) trapping of the oxygen-analogues (B-O and D-O) of both four-membered-ring intermediate B-S and ring-opening intermediate D-S, 3) deuterium labeling studies, and 4) theoretical studies. These results show that 1) the reaction rate-determining step is [2+2] cycloaddition, 2) the C=N bond cleavage takes place before C(sp(3))-H bond cleavage, 3) the hydrogen attached to C6 in 2-S originates from the carbodiimide, and 4) three types of new aza-heterocycles, such as 1,2-dihydrothiopyrimidines, N-acyl 2,3-dihydropyrimidinthiones, and 1,2-dihydropyrimidinamino acids are constructed efficiently based on 2-S. All results strongly support the idea that the reaction proceeds through [2+2] cycloaddition/4π electrocyclic ring-opening/1,5-H shift/6π electrocyclic ring-closing as key steps. The research strategy on the synthesis, isolation, and reactivity investigation of important intermediates in metal-mediated reactions not only helps achieve an in-depth understanding of reaction mechanisms but also leads to the discovery of new synthetically useful reactions based on the important intermediates.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking University, Beijing 100871, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Zhao
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yue
authors.initials: Y
authors.lastname: Chi
authors.forename: Zitao
authors.initials: Z
authors.lastname: Wang
authors.forename: Wen-Xiong
authors.initials: WX
authors.lastname: Zhang
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Xi
mesh_terms: D001385:Azetines / Q000737:chemistry; D002234:Carbodiimides / Q000138:chemical synthesis / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry; D018360:Crystallography, X-Ray; D061565:Cycloaddition Reaction; D003903:Deuterium / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry; D008968:Molecular Conformation; D009584:Nitrogen / Q000737:chemistry; D011789:Quantum Theory
chemical_list: D001385:Azetines; D002234:Carbodiimides; D002244:Carbon; D006859:Hydrogen; D003903:Deuterium; D009584:Nitrogen
keywords: CH activation; multicomponent reactions; reaction intermediates; reaction mechanisms; synthetic methods